The current grant studies clinical human transplantation (with the emphasis on renal transplantation) in an attempt to document the problems and to obtain potential solutions to those problems which can be answered by laboratory investigation. We are currently studying transplantation high-risk patients: diabetics, patients with metabolic disease, children and the aged. The clinical development of antilymphoblast globulin and correlation of clinical results with in vitro characteristics is well under way. Studies of histocompatibility typing, cross matching, and transplantation into patients with anti-HLA antibodies is now being analyzed. The clinical virological correlations between renal allograft rejection episodes and the reactivation of herpes viruses is being clarified. During these studies a particular attempt is made to determine the degree of non-specific immuno- incompetence induced by our immunosuppressive regimen, and the degree of specific immunologic unresponsiveness which might occur directed against donor tissues. The experimental animal studies are derived directly from our clinical work. Studies on the technology of the mixed lymphocyte culture have been combined with studies of the mixed lymphocyte culture during experimental allograft rejection in order to cast some light on the interpretation to be gained on such studies in man. These studies have led us to those involving the interactions of mitogens and the lymphocyte membrane. Our methods for the production for purification of human histocompatibility antigen are ultimately designed for the induction of tolerance to these antigens in man. Studies of organ preservation have shown that preservation of whole dog kidneys can be accomplished even during freezing to minus 20 degrees if suitable precautions are taken. Immunopathological construction of suitable models of renal disease will allow better understanding of recurrence of original disease in renal transplants.